Animal cells and enzymes lose function when damaged. This proposes research in practical methods for repair of the damage. The goal is to regain full catalytic activity of mammalian enzymes, and to regain cell function, after damage or denaturation. Three methods will be used to initially destroy activity or function: Thermal treatment, heating or freezing, chemical means, and organism death or cell storage. Preparation of separated cells from tissue will involve its own damage, and variability in separated cell preparations will be investigated. Treatment of heat damage of enzymes will employ methods developed here with organic cosolvents. The enzyme work will be extended to include high hydraulic pressure techniques and attempts to induce refolding by interaction with molecules which are similar to the substrates. Cell function will be measured by calorimetric heat measurements when the cells are mixed with substrates, allergens, hemagglutinating agents, and other cells to which they adhere. Repair of damaged cell systems will be attempted via some of the methods that work with enzymes. Also employed shall be biologically active compounds, e.g. steroids, which have major effects in membrane stabilization, as reviewed by Seeman in 1966. In collaborative work, phagocytic hemocytes from insects will be damaged, followed by an attempt to restore function. Assay of phagocytosis will also be carried out by monitoring heat production, upon mixing B. subtilis with the hemocytes. Mammalian leukocytes (neutrophils) will be similarly investigated.